Estradiol induces heparanase-1 expression and heparan sulfate proteoglycan degradation in the endometrium.

Department of General Surgery, Rush University Medical Center, Chicago, Illinois, United States
Human Reproduction (Impact Factor: 4.57). 05/2007; 22(4):927-37. DOI: 10.1093/humrep/del483
Source: PubMed


This study seeks to determine whether estrogen is able to regulate the expression of heparanase-1 (HPR1) in human endometrium.
HPR1 expression and heparan sulphate (HS) deposition in the endometrium collected in various menstrual phases were analysed by immunohistochemical and immunofluorescence staining, respectively. HPR1 expression in the endometrial cells unexposed or exposed to estradiol was analysed by using RT-PCR and luciferase reporter assay. HPR1 activity was analysed by using a novel enzyme-linked immunosorbent assay (ELISA). Cell surface HS levels were analysed by flow cytometry. Serum HPR1 activity in women receiving follicle-stimulating hormone (FSH) for IVF was measured by ELISA.
HPR1 expression was rarely detected in the endometrium in the early and mid-proliferative phases but was increased in the late proliferative phase and in the secretory phases. HPR1 expression was negatively associated with HS in the basement membrane (BM) of the endometrial glands. HPR1 gene expression, HPR1 promoter activity and HPR1 enzymatic activity were increased in the endometrial cells when exposed to 17beta-estradiol (E(2)), whereas cell surface HS levels showed a decrease which could be blocked by PI-88, an HPR1 inhibitor. Serum HPR1 levels were increased in women with moderately elevated blood estrogen levels after receiving FSH.
HPR1 is differentially expressed in the endometrium in different menstrual phases. Estrogen plays an important role in inducing HPR1 expression, subsequently leading to HS degradation on the endometrial cell surface and in the BM of the endometrium.

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Available from: Richard Prinz, Aug 08, 2014
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    • "There are three subfamilies of heparan sulphate proteoglycans (HSPGs): the membrane spanning proteoglycans (namely, syndecans, betaglycan and CD44v3), the glycophosphatidylinositol-linked proteoglycans (namely, glypicans) and the secreted ECM proteoglycans (namely agrin, collagen XVIII and perlecan) (Fig. 2). HSPGs are widely expressed throughout the reproductive tract, with evidence of them involved in the regulation of folliculogenesis (Rodgers et al., 2003), modulation of sperm viability and capacitation during sperm transport in the oviduct (Tienthai et al., 2000; Bergqvist and Rodriguez-Martinez, 2006), regulation of endometrial cycling (Potter and Morris, 1992; Kelly et al., 1995; San Martin et al., 2004; Germeyer et al., 2007; Lai et al., 2007; Xu et al., 2007), genital HIV transmission (Bobardt et al., 2007; Saidi et al., 2007), cervical neoplasia (Numa et al., 2002; Shinyo et al., 2003; Sobel et al., 2005) and vaginal growth (Cano-Gauci et al., 1999; Inki, 1997). These interactions primarily occur due to the properties of their heparan side chains; syndecan-3 on dendritic cells is capable of directly binding HIV-1 in a heparan suphate-dependent manner, thereby promoting transmission to T-cells (de Witte et al., 2007). "
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